An MS/MS analysis (tandem analysis) is widely used as a mass analysis method for the identification, structure analysis, quantitative determination, and other measurements of a compound having a large molecular weight. There are a variety of types of mass spectrometers for performing an MS/MS analysis. Among those, a tandem quadrupole mass spectrometer has a relatively simple device structure and is easy to operate and handle.
In a general tandem quadrupole mass spectrometer, ions originating from sample components which are generated in an ion source are introduced into an anterior quadrupole mass filter, where ions that have a specific mass-to-charge ratio m/z are selected as precursor ions. The precursor ions are introduced into a collision cell in which a quadrupole (or multipole for more than four poles) ion guide is provided. A collision induced dissociation (CID) gas such as argon is supplied to the inside of the collision cell. The precursor ions collide with the CID gas and are dissociated in the collision cell. As a result, a variety of product ions are generated. The product ions are introduced into a posterior quadrupole mass filter, where product ions that have a specific mass-to-charge ratio m/z are selected. The selected ions arrive at a detector to be detected.
A tandem quadrupole mass spectrometer as previously described is sometimes used alone, but it is often used in combination with a chromatograph such as a gas chromatograph (GC) or a liquid chromatograph (LC). Especially in recent years, chromatograph tandem quadrupole mass spectrometers have become essential in the field of microanalysis for analyzing a sample containing a number of compounds or a sample in which a variety of impurities are mixed, e.g. the detection of residual pesticides in food, the examination of environmental pollutants, the examination of drug levels in blood, and drug/toxicity screenings.
An MS/MS analysis in a chromatograph tandem quadrupole mass spectrometer includes several measurement modes such as an MRM (Multiple Reaction Monitoring) measurement mode, a precursor ion scan measurement mode, a product ion scan measurement mode, and a neutral loss scan measurement mode (refer to Patent Document 1). Of these, in an MRM measurement mode, the mass-to-charge ratio of the ions which are allowed to pass through the anterior quadrupole mass filter and that of the ions which are allowed to pass through the posterior quadrupole mass filter are fixed so that the intensity (amount) of the specific product ions generated by means of the dissociation of specific precursor ions is measured. Therefore, in an MRM measurement, two-stage mass filters eliminate non-measurement components, and ions and neutral particles derived from impurity components, this enabling the acquisition of an ion intensity signal with a high SN ratio. Therefore, an MRM measurement is a powerful technique, especially for the quantitative analysis of minor components. For example, in a gas chromatograph tandem quadrupole mass spectrometer (GC/MS/MS), an MRM measurement is often used for a simultaneous multicomponent quantitative analysis of residual pesticides and other analyses in which the quantitativity of the components is minute.
Performing an MRM measurement as previously described requires an appropriate setting of, prior to performing an analysis, the measurement conditions such as the mass-to-charge ratio of the precursor ions for the compounds to be measured, the mass-to-charge ratio of the product ions, and the collision energy in a CID operation. In a conventional chromatograph tandem quadrupole mass spectrometer, a product ion scan measurement mode is used to search measurement conditions (measurement parameters) of an MRM measurement. In the product ion scan measurement mode, the mass-to-charge ratio selected for the anterior quadrupole mass filter is fixed, while the mass-to-charge ratio of the ions which are allowed to pass through the posterior quadrupole mass filter is scanned across a predetermined range. More specifically, the measurement conditions of an MRM measurement are determined as in the following manner.
(1) First, in a chromatograph tandem quadrupole mass spectrometer, a simple scan measurement without a CID operation is repeated on a sample which contains a target compound so as to collect the mass spectrum data for a predetermined time range.
(2) Based on the collected data, a mass spectrum, a total ion chromatogram, or a mass chromatogram is created. An analyst analyzes it to obtain the retention time of the target compound and the mass-to-charge ratio which characterizes the target compound.
(3) Subsequently, a product ion scan measurement is performed on the sample which contains the target compound in a predetermined time range near the retention time of the compound so as to repeatedly collect the MS2 spectrum data. In the product ion scan measurement, the mass-to-charge ratio which characterizes the compound is specified as the mass-to-charge ratio of the precursor ions. In the MS2 spectrum, peaks corresponding to a variety of product ions originating from the target compound are observed.
(4) When the collision energy is changed, the mode of the dissociation is changed, which consequently changes the pattern of the observed product ions. In view of this, every time the collision energy is changed by a predetermined level, the product ion scan measurement as described in Step (3) is performed to collect the MS2 spectrum data. Then the analyst examines the MS2 spectrum data to determine the appropriate value of the mass-to-charge ratio for the product ions corresponding to the target compound and the value of the collision energy. The determined values are set as the MRM measurement conditions.
When performing a simultaneous multicomponent quantitative analysis, it is necessary to set beforehand the MRM measurement conditions for all the compounds to be quantitatively determined. This requires the measurement and data processing of Steps (3) and (4) for each of the components. Therefore, each compound requires an appropriate determination of the measurement time range in which a product ion scan measurement is performed, and of the mass-to-charge ratio range across which a scan is performed in the product ion scan measurement. However, in a simultaneous multicomponent analysis, it is not unusual that the number of target compounds is 100 or more. In such cases, it is a troublesome and heavy burden for the analyst to determine the appropriate measurement time range and mass-to-charge ratio range for each of the compounds and to manually enter the determined values.
In the case where two compounds have retention times close to each other, for example, if one end of the measurement time range for a product ion scan measurement is placed between the two peaks, the peaks of the chromatogram will appear very close to the end of the measurement time range. In this case, even a minor shift of the retention time when a measurement sample is actually measured causes the end of the measurement time range to enter the peak range of the chromatogram. This might impede the acquisition of the correct MS2 spectrum and the extraction of appropriate product ions. An appropriate setting of the measurement time range of the product ion scan measurement is required in order to avoid this problem. However, this is a very difficult operation.
For a general chromatograph mass spectrometer, Patent Document 2 discloses a technique aiming to reduce the time and labor for setting the measurement conditions for a scan/SIM (Selected Ion Monitoring) simultaneous measurement. However, the technique described in Patent Document 2 is used for determining the measurement time range and other values for a scan/SIM simultaneous measurement using a general chromatograph mass spectrometer, not a tandem quadrupole mass spectrometer. Hence, the technique is not suitable for determining the measurement conditions for a product ion scan measurement for the sake of the determination of the MRM measurement parameters by means of a chromatograph tandem quadrupole mass spectrometer.